1. Field of the Invention
The present invention concerns a method for making antibodies which can, for example, be used for cancer diagnosis or therapy. The invention further provides a method for identifying an antigen which is differentially expressed on the surface of distinct cell populations. The present invention additionally provides human antibodies directed against decay accelerating factor (DAF), as well as therapeutic compositions comprising such antibodies. Moreover, the invention pertains to a method of treating lung cancer with antibodies directed against DAF.
2. Description of Related Art
The demonstration of significant anti-tumor efficacy of antibodies has long been sought-after in the clinic and recently obtained using “naked” chimeric/humanized antibodies (Riethmüller et al., Lancet, 343: 1177-1183 (1994); Riethmüller et al., J. Clin. Oncol., 16: 1788-1794 (1998); Maloney et al., Blood, 90: 2188-2195 (1997); McLaughlin et al., J. Clin. Oncol., 16: 2825-2833 (1998); and Baselga et al., J. Clin. Oncol., 14: 697-699 (1996)) antibodies as well as with radiolabeled murine antibodies (Press et al., N. Engl. J. Med., 329: 1219-1224 (1993); Press et al., Lancet, 346: 336-340, (1995); Kaminski et al., N. Engl. J. Med., 329: 459-495 (1993); Kaminski et al., J. Clin. Oncol., 14: 1974-1981 (1996)). Indeed a chimeric anti-CD20 antibody (Reff et al., Blood, 83: 435-445 (1994)) and a chimeric/humanized anti-HER2 antibody (Carter et al. PNAS (USA) 89:4285-4289 (1992)) have recently been approved by US Federal Drug Administration for the treatment of non-Hodgkin's lymphoma and metastatic breast cancer, respectively. These successes with anti-tumor antibodies in patients has led to renewed interest in the identification of novel tumor-associated antigens suitable for antibody targeting.
The traditional approach to obtaining tumor-specific antibodies has been to immunize mice with tumor cells and to screen the resultant monoclonal antibodies for their binding specificity. Unfortunately tumor-binding antibodies obtained in this way often cross-react with many normal cells, which may interfere with their clinical utility. Ideally one would like to select rather than screen for antibodies that bind selectively to tumor. The advent of antibody fragment display on phage (McCafferty et al., Nature, 348: 552-554 (1990)) and the development of large (>1010 clone) phage display libraries (Griffiths et al., EMBO J., 13:3245-3260 (1994), Vaughan et al. Nat. Biotechnol. 14: 309-314 (1996)) offers a potential way of making antibodies. With antibody phage screening, unlike hybridoma technology, it is readily possible to obtain antibodies binding antigens that are highly conserved between mouse and man (Nissim et al., EMBO J., 13:692-698 (1994)).
Naïve antibody phage libraries have proved to be a rapid and general method for identifying antibodies binding to purified antigens (Griffiths et al., EMBO J., 13:3245-3260 (1994); Vaughan et al. Nat. Biotechnol. 14: 309-314 (1996); Nissim et al., EMBO J., 13:692-698 (1994)). In contrast, panning cellular targets with antibody phage has proved much more difficult because of the much lower effective antigen concentration, greater antigen complexity and the tendency of phage to bind non-specifically to cells. Nevertheless, antibodies against cell surface antigens have been identified (Marks et al, Bio/Technol., 11: 1145-1149 (1992); Portolano et al., J. Immunol., 151:2839-2851 (1993); de Kruif et al, Proc. Natl. Acad. Sci. USA, 92:3938-3942 (1995); Van Ewijk et al., Proc. Natl. Acad. Sci. USA, 94:3903-3908 (1997); Cai et al, Proc. Natl. Acad. Sci. USA, 92:6537-6541 (1995); Cai et al Proc. Natl. Acad. Sci. USA, 93:6280-6285 (1996); Cai et al, Proc. Natl. Acad. Sci. USA, 94:9261-9266 (1997)). Melanoma specific antibodies have been identified by selecting for antibody phage that bind to melanoma cells but not melanocytes using antibody phage libraries constructed from human donors immunized with their own tumor cells (Cai et al, Proc. Natl. Acad. Sci. USA, 92:6537-6541 (1995); Cai et al Proc. Natl. Acad. Sci. USA, 93:6280-6285 (1996); Cai et al., Proc. Natl. Acad. Sci. USA, 94:9261-9266 (1997)).
Decay Accelerating Factor (DAF), is a GPI-anchored protein that acts together with two other GPI-anchored proteins, CD46 and CD59, in protecting host cells from complement-mediated cell lysis (Nicholson-Weller et al. J. Lab. Clin. Med., 123:485-491 (1994)). DAF is expressed at widely varying levels on tumor cell lines and its overexpression correlates with enhanced resistance to complement-mediated cell lysis in vitro (Cheung et al., J. Clin. Invest., 81:1122-1128 (1988)). DAF overexpression has been observed on a variety of human tumor tissues including 6/9 lung adenocarcinomas and 2/7 lung squamous cell carcinomas (Niehans et al., Am. J. Path., 149:129-142 (1996)). Regarding normal lung tissue, DAF has been detected by immunohistochemistry on the alveolar epithelium, interstitium and endothelium as well as the bronchial epithelium, glands and ducts plus blood vessels (Niehans et al., Am. J. Path., 149:129-142 (1996)).
Other publications relating to DAF include Hara et al. Immunology Letters 37:145-152 (1993); Nicholson-Weller and Wang J. Lab. Clin. Med. 123(4):485491 (1994); Lublin et al. J. Immunol. 137:1629-1635 (1986); WO99/43800; WO98/39659; U.S. Pat. No. 5,695,945; U.S. Pat. No. 5,763,224; and WO 86/07062.
Vollmers et al. Cancer Research 49: 2471-2476 (1989); and Vollmers et al. Cancer 76(4): 550-558 (1995) describe the human IgM monoclonal antibody “SC-1” which is said inhibit growth of stomach adenocarcinoma cells in vitro and in vivo by inducing apoptosis. Vollmers et al. Oncology Reports 5:549-552 (1998) reports the results of a clinical trial in which patients with poorly differentiated stomach adenocarcinoma were treated with the SC-1 antibody. The later publication, Hensel et al. Cancer Research 59:5299-5306 (1999), identifies DAF as the antigen bound by SC-1.